High BCG Vaccination Coverage Research Articles

Does BCG vaccine prevent contract and severity of COVID-19 infection in India? A situational analysis

Background: The COVID-19 pandemic has created worldwide emergency with morbidities, mortality and panic. The BCG vaccine, usually given to prevent childhood tuberculosis, surfaced as an option as suggested by some ecological observations. However, some others studies could not establish and explain the protective effects of BCG vaccination against COVID-19 pandemic. India is one country with high BCG vaccination coverage and is among the countries with lowest COVID-19 case fatality rate. Aims and Objectives: We examine the relationship between the BCG coverage and COVID-19 burden in various states/UTs of India. Materials and methods: The information on BCG coverage and morbidity and mortality of COVID-19 was obtained from NFHS and www.covid19India.org respectively. Results: The analysis suggested very weak positive relationship of BCG coverage with cases and deaths due to COVID-19. Moderate positive relationship was observed between BCG coverage and COVID-19 case fatality rate even after adjusting for health system performance. Conclusion: The conclusion of the study is against the role of BCG vaccination in containing the COVID-19 pandemic. The positive correlation which is not significant may be spurious and affected by many confounding factors like co-morbid conditions, testing strategies, population level immunity for other viral infections etc. Hence, the states and UTs should not be complacent by the hypothesized role of BCG vaccine in COVID-19 control. Rather, they should continue with the principles of social distancing, contact tracing, treating and surveillance of COVID-19.

Retesting the hypothesis that early Diphtheria-Tetanus-Pertussis vaccination increases female mortality: An observational study within a randomised trial

BackgroundThere are worrying indications that diphtheria-tetanus-pertussis (DTP) vaccine has negative non-specific effects for females. We previously found, in a trial of early-Bacillus Calmette-Guérin (BCG) to low weight (LW) neonates, that receiving early-DTP (before 2 months of age), was associated with increased female mortality compared with no-DTP/delayed-DTP. Within a subsequent LW trial, we aimed to retest this observation. MethodsBetween 2010 and 2014, in Guinea-Bissau, 2,398 infants were randomised 1:1 to early-BCG (intervention) or delayed-BCG (standard practice for LW neonates) and visited at 2, 6 and 12 months of age to assess nutritional and vaccination status. DTP is recommended at 6 weeks of age. We examined the effect of having “early-DTP” versus “no-DTP” at the time of the 2-month visit on all-cause mortality between the 2- and 6-month visits in Cox models stratified by sex and adjusted for BCG-group and 2-month-weight-for-age (z-scores) providing adjusted mortality rate ratios (aMRRs). We analysed to which extent conditions varied between the present and the previous LW trials and how that might have affected the overall result of comparing the early-DTP and the no-DTP groups. ResultsAt the time of the 2-month visit, 75% (1,795/2,398) had received DTP. Those vaccinated had better anthropometric indices than no-DTP infants at birth and by 2 months of age. Between the 2- and 6-month visits, 29 deaths occurred. The early-DTP/no-DTP aMRR was 1.09 (95% CI: 0.44–2.69); 1.19 (0.45–3.15) for females and 0.77 (0.14–4.19) for males. Compared to the previous study, the present study cohort had 56% (30–72%) lower overall mortality, fewer no-DTP infants, higher BCG vaccination coverage and several more oral polio vaccine campaigns. ConclusionWe did not find that early-DTP was associated with increased female mortality as found in a previous study; differences in results may partly be due to a decline in overall mortality and changes in vaccination practices.

Significantly Improved COVID-19 Outcomes in Countries with Higher BCG Vaccination Coverage: A Multivariable Analysis.

The COVID-19 pandemic that started in China has spread within 3 months to the entire globe. We tested the hypothesis that the vaccination against tuberculosis by Bacille Calmette–Guérin vaccine (BCG) correlates with a better outcome for COVID-19 patients. Our analysis covers 55 countries complying with predetermined thresholds on the population size and number of deaths per million (DPM). We found a strong negative correlation between the years of BCG administration and the DPM along with the progress of the pandemic, corroborated by permutation tests. The results from multivariable regression tests with 23 economic, demographic, health-related, and pandemic restriction-related quantitative properties, substantiate the dominant contribution of BCG years to the COVID-19 outcomes. The analysis of countries according to an age-group partition reveals that the strongest correlation is attributed to the coverage in BCG vaccination of the young population (0–24 years). Furthermore, a strong correlation and statistical significance are associated with the degree of BCG coverage for the most recent 15 years, but no association was observed in these years for other broadly used vaccination protocols for measles and rubella. We propose that BCG immunization coverage, especially among the most recently vaccinated population, contribute to attenuation of the spread and severity of the COVID-19 pandemic.

Immunodiagnostic Potential of an In-Vitro Interferon-Gamma Release Assay for Latent Tuberculosis Infection Among Apparently Healthy Individuals in Okada Community, Nigeria

A major challenge in the global Tuberculosis (TB) control is the diagnosis and treatment of Latent Tuberculosis Infection (LTBI). In the absence of any reference standard test for the diagnosis of LTBI, this study set out to compare the performance of the two current immune-based tests, Tuberculin Skin Test (TST) and Quantiferon–TB Gold In–Tube (QFT-GIT) ELISA in the diagnosis of LTBI. Two sets of diagnostic results for 196 apparently healthy volunteers from a cross-section of Okada Community, Edo State, Nigeria were compared in terms of age, occupation, BCG-vaccination status, prior TST and cigarette smoking history. Overall, 56 (28.6%) and 81 (41.3%) of the subjects were diagnosed with LTBI by the QFT-GIT test and TST respectively. The LTBI prevalence as assessed by the QFT-GIT test was significantly higher among the non-BCG-vaccinated, compared to the BCG-vaccinees (X²=18.79, df=1, p=0.0001). The highest concordance (QFT-GIT+ve/TST+ve) was found in the occupation categories (Ʀ=-0.009, p=0.747) and the highest discordance(QFT-GIT –ve/TST +ve) was with respect to the BCG-vaccination status (Ʀ=-0.194, p=0.046).The disparity in the performance of the two tests is attributable to the high false – positive TST results, which is a direct reflection of high (90.8%) BCG vaccination level among the study population. It is advocated that the two-step testing approach, using the QFT-GIT assay as a confirmatory test for LTBI after initial positive screening by the TST, be introduced into the TB control strategy in TB – laden communities with high BCG vaccination coverage.

Family history of immigration from a tuberculosis endemic country and low family income are associated with a higher BCG vaccination coverage in Ile-de-France region, France

After withdrawal of multipuncture BCG device from the French market in January 2006, vaccination coverage (VC) with the intradermal device has dropped and since remained sub-optimal in Ile-de-France, the only region of mainland France where BCG is recommended to all children. We conducted a cross-sectional study to identify socio-economic factors associated with BCG VC in children of Paris metropolitan area born after January 2006. Two-stage random sampling was used to include 425 children up to 5 years old from Paris and its suburbs. Information was collected through face-to-face interviews and vaccination status confirmed by a vaccination document. Poisson regression analyzed the association between VC and potential determinants. VC of children from families with the lowest incomes (first quartile of family income/consumption unit (CU) (<883 €) was close to 100% regardless of family origin. In families with higher incomes (≥883 €/CU), VC was significantly higher among children born to families from a tuberculosis highly endemic country (98.2%) compared with other children (76.2%) (p=0.004). Children of low socio-economic background as well as those with a family history of immigration, regardless of family income, are correctly identified as being at high risk of tuberculosis and properly vaccinated with BCG in this area.

Annual risk of tuberculosis infection in Sri Lanka: a low prevalent country with a high BCG vaccination coverage in the South-East Asia Region.

Despite its simplicity, efficiency and reliability, Sri Lanka has not used the Annual Risk of Tuberculosis Infection (ARTI) to assess the prevalence and efficiency of tuberculosis (TB) control. Hence, a national tuberculin survey was conducted to estimate the ARTI. A school-based, cross-sectional tuberculin survey of 4352 children aged 10 years irrespective of their BCG vaccination or scar status was conducted. The sample was selected from urban, rural and estate strata using two-stage cluster sampling technique. In the first stage, sectors representing three strata were selected and, in the second stage, participants were selected from 120 clusters. Using the mode of the tuberculin reaction sizes (15 mm) and the mirror-image technique, the prevalence and the ARTI were estimated. The prevalence of TB estimated for urban, rural and estate sectors were 13.9%, 2.2% and 2.3%, respectively. The national estimate of the prevalence of TB was 4.2% (95% CI = 1.7-7.2%). ARTI for the urban, rural and estate sectors were 1.4%, 0.2% and 0.2%, respectively, and the national estimate was 0.4% (95% CI = 0.2-0.7%). The estimated annual burden of newly infected or re-infected TB cases with the potential of developing into the active disease (400/100 000 population) was nearly 10-fold higher than the national new case detection rate (48/100 000 population). The national estimate of ARTI was lower than the estimates for many developing countries. The high-estimated risk for the urban sector reflected the need for intensified, sector-specific focus on TB control activities. This underscores the need to strengthen case detection. Repeat surveys are essential to determine the annual decline rate of infection.

Seroreactivity to new Mycobacterium leprae protein antigens in different leprosy-endemic regions in Brazil

New Mycobacterium leprae protein antigens can contribute to improved serologic tests for leprosy diagnosis/classification and multidrug therapy (MDT) monitoring. This study describes seroreactivity to M. leprae proteins among participants from three highly endemic leprosy areas in Brazil: central-western Goiânia/Goiás (GO) (n = 225), Rondonópolis/Mato Grosso (MT) (n = 764) and northern Prata Village/Pará (PA) (n = 93). ELISA was performed to detect IgG to proteins (92f, 46f, leprosy IDRI diagnostic-1, ML0405, ML1213) and IgM to phenolic glycolipid-I (PGL-I). Multibacillary (MB) leprosy had positive rates for PGL-I that were similar to those for proteins; however, some anti-PGL-I-negative subjects were positive for proteins, suggesting that adding protein antigen to PGL-I can enhance the sensitivity of MB leprosy detection. In MT, different degrees of seroreactivity were observed and ranked for MB, former patients after MDT, paucibacillary (PB) leprosy, household contact (HHC) and endemic control (EC) groups. The seroreactivity of PB patients was low in GO and MT. HHCs from different endemic sites had similar IgG antibody responses to proteins. 46f and 92f were not recognised by most tuberculosis patients, ECs or HHCs within GO, an area with high BCG vaccination coverage. Low positivity in EC and HHC was observed in PA and MT. Our results provide evidence for the development of an improved serologic test that could be widely applicable for MB leprosy testing in Brazil.

Tuberculin reactivity in bacille calmette-guerin vaccinated individuals with sputum positive pulmonary tuberculosis

The study was carried out to assess the value of tuberculin skin test for the diagnosis of Tuberculosis (TB) in BCG vaccinated individuals and to find out the sensitivity rate of tuberculin skin test (TST) in comparison to acid fast bacilli positive pulmonary TB. Similar population with high BCG vaccination coverage having both pulmonary TB patients (n=150) and apparently healthy individuals (n=150) in eastern Nepal were enrolled in this comparative study. Sputum from all the subjects was subjected to Z-N microscopy. TST was performed on these subjects by standard Mantoux method. Among the patients (mean age 36.18±14.15 yrs) and controls (mean age 35.61±13.44 yrs), 55.33 % and 47.33 % respectively have been found to be positive PPD reactors (&gt;10mm) which is statistically not significant (P&gt;0.05). About 23% of the patients &amp; 27% of controls failed to react (anergic) to 5 TU PPD. PPD reactivity rate was high in the patients whose sputum smears were graded as 1+ in Z-N microscopy. The sensitivity of TST was highest for the induration of &gt;5mm (77.3%). Specificity increased with increasing size of induration and was highest (73.3%) with induration of &gt;15 mm. Tuberculin skin test is an all or none phenomenon. In Nepal, tuberculin test has a limited value in the diagnosis of pulmonary TB as both the apparently healthy individuals and patients with sputum smear positive pulmonary TB who had been immunized with BCG, showed almost similar rate of tuberculin reactivity. DOI: http://dx.doi.org/10.3126/jcmsn.v7i1.5970 JCMSN 2011; 7(1): 28-35

Tuberculin Survey to Estimate the Prevalence of Tuberculosis Infection of the Elementary Schoolchildren under High BCG Vaccination Coverage

Background: Although the prevalence of tuberculosis infections (PTBI) is one of the basic epidemiologic indices, no survey has been carried out since 1995 because the nation-wide tuberculosis prevalence survey was changed to a surveillance system. Subjects without a BCG scar are examined in a tuberculin survey. However, it is very difficult to select these subjects under high vaccination coverage. It is important to evaluate the impact of BCG vaccinations on the tuberculin response and estimate the PTBI regardless of the BCG vaccination status. Methods: A nation-wide, school-based cross-sectional tuberculin survey was carried out among first graders in elementary school in 2006. A total of 5,148 children in 40 schools were selected by quota sampling. Tuberculin testing with 0.1 ml of two tuberculin units of PPD RT23 was carried out on 4,018 children. The maximum transverse diameter of induration was measured 48 to 72 hours later. The presence of a BCG scar was checked separately. Results: There were no BCG scars in 6.3% of the subjects. The mean induration size of tuberculin testing was , which included 1,882 (46.8%) subjects with an induration size of 0 mm. The PTBI was 10.9% (439 subjects) using a cut-off point of (conventional method). The annual risk of tuberculosis infections (ARTI) was 1.9% when the mean age of the subjects was assumed to be 6 years. There was no difference in the PTBI according to the presence or absence of a BCG scar [11.2% vs 7.6% (OR: 1.54, 95% CI: 0.98~2.43)]. Using a mirror image technique with 16 mm as the cut-off point, the PTBI and ARTI had decreased to 2.4% and 0.4% respectively. Conclusion: PTBI and ARTI, as estimated by conventional methods, appear to be high among BCG vaccinated children. A mirror image technique is more suitable for estimating the indices in a country with an intermediate burden of tuberculosis than the conventional method.

Analysis of latent tuberculosis and mycobacterium avium infection data using mixture models

BackgroundEstimation of the frequency of latent tuberculosis infection (LTBI) is difficult in areas with low tuberculosis infection rates and high exposure to non-tuberculous mycobacteria (NTM), including BCG vaccination. The objective was to assess LTBI and M avium infection and to estimate their probability based on skin tests responses in an infant population from a region with the aforementioned characteristics.MethodsA population-based tuberculin skin test (TST) and sensitin (M avium) survey was conducted on seven years old infants in Biscay, a province from The Basque Country (Spain). 2268 schoolchildren received sensitin and 5277 TST. Participation rate was 89%. Commonly used estimation methods were compared with a method based on the fit of mixture models using the Expectation Maximization algorithm. Functions estimating the probabilities of LTBI and M avium infection given the observed skin tests responses were developed for vaccinated and unvaccinated children.ResultsLTBI prevalences varied widely according to the estimation method. The mixture model provided prevalences higher than expected although intermediates between those obtained by currently recommended approaches. Exposure to previous BCG vaccine produces an upward shift of an average of about 3 mm on the induration size to attain the same probability of infection.ConclusionOur results confirm the commonplace exposure to NTM which effect should be taken into account when performing and assessing tuberculin surveys. The use of mixture analysis under the empirical Bayes framework allows to better estimate the probability of LTBI in settings with presence of other NTM and high BCG-vaccination coverage. An estimation of the average effect of BCG vaccination on TST induration is also provided. These models maximise information coming from classical tuberculin surveys and could be used together with the newly developed blood tests to improve survey's specificity and cost-effectiveness.

Tuberculin reactivity in a population of schoolchildren with high BCG vaccination coverage.

To investigate the influence of BCG vaccination or revaccination on tuberculin skin test reactivity, in order to guide the correct interpretation of this test in a setting of high neonatal BCG vaccination coverage and an increasing BCG revaccination coverage at school age. We conducted tuberculin skin testing and BCG scar reading in 1 148 children aged 7-14 years old in the city of Salvador, Bahia, Brazil. We measured the positive effect of the presence of one or two BCG scars on the proportion of tuberculin skin test results above different cut-off levels (induration sizes of > or = 5 mm, > or = 10 mm, and > or = 15 mm) and also using several ranges of induration size (0, 1-4, 5-9, 10-14, and > or = 15 mm). We also measured the effects that age, gender, and the school where the child was enrolled had on these proportions. The proportion of tuberculin results > or = 10 mm was 14.2% (95% confidence interval (CI) = 8.0%-20.3%) for children with no BCG scar, 21.3% (95% CI = 18.5%-24.1%) for children with one BCG scar, and 45.0% (95% CI = 32.0%-58.0%) for children with two BCG scars. There was evidence for an increasing positive effect of the presence of one and two BCG scars on the proportion of results > or = 5 mm and > or = 10 mm. Similarly, there was evidence for an increasing positive effect of the presence of one and two scars on the proportion of tuberculin skin test results in the ranges of 5-9 mm and of 10-14 mm. The BCG scar effect on the proportion of results > or = 5 mm and > or = 10 mm did not vary with age. There was no evidence for BCG effect on the results > or = 15 mm. In Brazilian schoolchildren, BCG-induced tuberculin reactivity is indistinguishable, for results under 15 mm, from reactivity induced by Mycobacterium tuberculosis infection. BCG revaccination at school age increases the degree of BCG-induced tuberculin reactivity found among schoolchildren. This information should be taken into account in tuberculin skin test surveys intended to estimate M. tuberculosis prevalence or to assess transmission patterns as well as in tuberculin skin testing of individuals used as an auxiliary tool in diagnosing tuberculosis. Taking this information into consideration is especially important when there is increasing BCG revaccination coverage.

Using lot quality assurance sampling to improve immunization coverage in Bangladesh.

To determine areas of low vaccination coverage in five cities in Bangladesh (Chittagong, Dhaka, Khulna, Rajshahi, and Syedpur). Six studies using lot quality assurance sampling were conducted between 1995 and 1997 by Basic Support for Institutionalizing Child Survival and the Bangladesh National Expanded Programme on Immunization. BCG vaccination coverage was acceptable in all lots studied; however, the proportion of lots rejected because coverage of measles vaccination was low ranged from 0% of lots in Syedpur to 12% in Chittagong and 20% in Dhaka's zones 7 and 8. The proportion of lots rejected because an inadequate number of children in the sample had been fully vaccinated varied from 11% in Syedpur to 30% in Dhaka. Additionally, analysis of aggregated, weighted immunization coverage showed that there was a high BCG vaccination coverage (the first administered vaccine) and a low measles vaccination coverage (the last administered vaccine) indicating a high drop-out rate, ranging from 14% in Syedpur to 36% in Dhaka's zone 8. In Bangladesh, where resources are limited, results from surveys using lot quality assurance sampling enabled managers of the National Expanded Programme on Immunization to identify areas with poor vaccination coverage. Those areas were targeted to receive focused interventions to improve coverage. Since this sampling method requires only a small sample size and was easy for staff to use, it is feasible for routine monitoring of vaccination coverage.

Leprosy: The Beginning of an End to a Public Health Problem?

Incidence rates of leprosy seem to be falling in most countries around the world, despite the HIV epidemic. Among the reasons for the declining rates are changing socioeconomic conditions and high BCG vaccination coverage. The numbers of people disabled by leprosy, however, are more important than incidence rates of leprosy per se. The issue of the disabled will remain a public health problem for many decades to come.